Sox17 drives functional engraftment of endothelium converted from non-vascular cells

William Schachterle, Chaitanya R. Badwe, Brisa Palikuqi, Balvir Kunar, Michael Ginsberg, Raphael Lis, Masataka Yokoyama, Olivier Elemento, Joseph M. Scandura () and Shahin Rafii ()
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William Schachterle: Ansary Stem Cell Institute, Weill Cornell Medicine
Chaitanya R. Badwe: Ansary Stem Cell Institute, Weill Cornell Medicine
Brisa Palikuqi: Ansary Stem Cell Institute, Weill Cornell Medicine
Balvir Kunar: Ansary Stem Cell Institute, Weill Cornell Medicine
Michael Ginsberg: Angiocrine Bioscience
Raphael Lis: Ansary Stem Cell Institute, Weill Cornell Medicine
Masataka Yokoyama: Ansary Stem Cell Institute, Weill Cornell Medicine
Olivier Elemento: HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College
Joseph M. Scandura: Ansary Stem Cell Institute, Weill Cornell Medicine
Shahin Rafii: Ansary Stem Cell Institute, Weill Cornell Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.

Date: 2017
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DOI: 10.1038/ncomms13963

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